PDF(Pubmed)
Abstract：
The mammalian cerebral cortex shows functional specialization into regions with distinct neuronal compositions, most strikingly in the human brain, but little is known in about how cellular lineages shape cortical regional variation and neuronal cell types during development. Here, we use somatic single nucleotide variants (sSNVs) to map lineages of neuronal sub-types and cortical regions. Early-occurring sSNVs rarely respect Brodmann area (BA) borders, while late-occurring sSNVs mark neuron-generating clones with modest regional restriction, though descendants often dispersed into neighboring BAs. Nevertheless, in visual cortex, BA17 contains 30-70% more sSNVs compared to the neighboring BA18, with clones across the BA17/18 border distributed asymmetrically and thus displaying different cortex-wide dispersion patterns. Moreover, we find that excitatory neuron-generating clones with modest regional restriction consistently share low-mosaic sSNVs with some inhibitory neurons, suggesting significant co-generation of excitatory and some inhibitory neurons in the dorsal cortex. Our analysis reveals human-specific cortical cell lineage patterns, with both regional inhomogeneities in progenitor proliferation and late divergence of excitatory/inhibitory lineages.
摘要：
哺乳动物大脑皮层显示出具有不同神经元成分的区域的功能特化，在人脑中最引人注目的是，但是在发育过程中，细胞谱系如何塑造皮质区域变异和神经元细胞类型方面知之甚少。这里,我们使用体细胞单核苷酸变异体(sSNV)绘制神经元亚型和皮质区域的谱系图.早期发生的sSNV很少尊重Brodmann区域（BA）边界，虽然晚期发生的sSNV标记神经元生成克隆具有适度的区域限制，尽管后代经常分散到邻近的BAs中。然而，在视觉皮层，与邻近的BA18相比,BA17含有多30-70%的sSNV,其中跨越BA17/18边界的克隆不对称地分布并且因此显示不同的皮质宽分散模式。此外，我们发现，具有适度区域限制的兴奋性神经元生成克隆始终与一些抑制性神经元共享低马赛克sSNV，提示背侧皮质中兴奋性和一些抑制性神经元的显著协同生成。我们的分析揭示了人类特定的皮层细胞谱系模式，祖细胞增殖的区域不均匀性和兴奋性/抑制性谱系的晚期分歧。
